Epilepsy and depression are 2 of the most common neurological diseases. Although the manifestations of these diseases are distinct, there is compelling evidence that they share common underlying mechanisms. (1) Epidemiological studies demonstrate that depression is the most common comorbid psychiatric disorder in patients with epilepsy, and patients with major depression also have a higher frequency of epilepsy. (2) Some anticonvulsant therapies, such as valproic acid and vagus nerve stimulation, are also effective in treating affective disorders. The interaction between epilepsy and depression has not been empirically studied in animal models, and the common molecular mechanism(s) underlying these 2 diseases have not been identified. The goal of this proposal is to use rodent behavioral models to further investigate the link between epilepsy and depression. Our preliminary data indicate that rats selectively bred for susceptibility or resistance to depression-like phenotypes also have alterations in seizure susceptibility, suggesting that these rats are a good model to study genes that influence both phenotypes. In Aim 1 of this proposal, we will further characterize and validate the seizure susceptibility phenotype of our selectively bred rats. In Aim 2, we will genetically characterize our 6 selectively bred rat strains using genome-wide microsatellite markers. Completion of these aims will develop animal models with which to study epilepsy and depression comorbidity and lay the groundwork for identification of genes that contribute to both diseases.